Whole-genome sequence variation, population structure and demographic history of the Dutch population (original) (raw)
References
- Lander, E.S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).
Article CAS PubMed Google Scholar - Hinds, D.A. et al. Whole-genome patterns of common DNA variation in three human populations. Science 307, 1072–1079 (2005).
Article CAS PubMed Google Scholar - International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).
- International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007).
- International HapMap 3 Consortium. Integrating common and rare genetic variation in diverse human populations. Nature 467, 52–58 (2010).
- Manolio, T.A. Bringing genome-wide association findings into clinical use. Nat. Rev. Genet. 14, 549–558 (2013).
Article CAS PubMed Google Scholar - Visscher, P.M., Brown, M.A., McCarthy, M.I. & Yang, J. Five years of GWAS discovery. Am. J. Hum. Genet. 90, 7–24 (2012).
CAS PubMed PubMed Central Google Scholar - McClellan, J. & King, M.-C. Genetic heterogeneity in human disease. Cell 141, 210–217 (2010).
Article CAS PubMed Google Scholar - Gibson, G. Rare and common variants: twenty arguments. Nat. Rev. Genet. 13, 135–145 (2011).
Article CAS Google Scholar - Goldstein, D.B. et al. Sequencing studies in human genetics: design and interpretation. Nat. Rev. Genet. 14, 460–470 (2013).
Article CAS PubMed PubMed Central Google Scholar - Weischenfeldt, J., Symmons, O., Spitz, F. & Korbel, J.O. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat. Rev. Genet. 14, 125–138 (2013).
Article CAS PubMed Google Scholar - Veltman, J.A. & Brunner, H.G. De novo mutations in human genetic disease. Nat. Rev. Genet. 13, 565–575 (2012).
CAS PubMed Google Scholar - Fu, W. et al. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 493, 216–220 (2013).
Article CAS PubMed Google Scholar - Gravel, S. et al. Demographic history and rare allele sharing among human populations. Proc. Natl. Acad. Sci. USA 108, 11983–11988 (2011).
Article PubMed PubMed Central Google Scholar - Mathieson, I. & McVean, G. Differential confounding of rare and common variants in spatially structured populations. Nat. Genet. 44, 243–246 (2012).
Article CAS PubMed PubMed Central Google Scholar - Boomsma, D.I. et al. The Genome of the Netherlands: design, and project goals. Eur. J. Hum. Genet. 22, 221–227 (2014).
Article CAS PubMed Google Scholar - Brandsma, M. et al. How to kickstart a national biobanking infrastructure—experiences and prospects of BBMRI-NL. Nor. Epidemiol. 21, 143–148 (2012).
Google Scholar - DePristo, M.A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011).
Article CAS PubMed PubMed Central Google Scholar - Menelaou, A. & Marchini, J. Genotype calling and phasing using next-generation sequencing reads and a haplotype scaffold. Bioinformatics 29, 84–91 (2013).
Article CAS PubMed Google Scholar - 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56–65 (2012).
- MacArthur, D.G. et al. A systematic survey of loss-of-function variants in human protein-coding genes. Science 335, 823–828 (2012).
Article CAS PubMed PubMed Central Google Scholar - Tennessen, J.A. et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337, 64–69 (2012).
Article CAS PubMed PubMed Central Google Scholar - Kiezun, A. et al. Exome sequencing and the genetic basis of complex traits. Nat. Genet. 44, 623–630 (2012).
Article CAS PubMed PubMed Central Google Scholar - Petrovski, S., Wang, Q., Heinzen, E.L., Allen, A.S. & Goldstein, D.B. Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet. 9, e1003709 (2013).
Article CAS PubMed PubMed Central Google Scholar - Stenson, P.D. et al. The Human Gene Mutation Database: 2008 update. Genome Med. 1, 13 (2009).
Article CAS PubMed PubMed Central Google Scholar - Cooper, D.N., Krawczak, M., Polychronakos, C., Tyler-Smith, C. & Kehrer-Sawatzki, H. Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum. Genet. 132, 1077–1130 (2013).
Article CAS PubMed PubMed Central Google Scholar - Cassa, C.A., Tong, M.Y. & Jordan, D.M. Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals. Hum. Mutat. 34, 1216–1220 (2013).
Article PubMed PubMed Central Google Scholar - Dorschner, M.O. et al. Actionable, pathogenic incidental findings in 1,000 participants' exomes. Am. J. Hum. Genet. 93, 631–640 (2013).
Article CAS PubMed PubMed Central Google Scholar - McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).
Article CAS PubMed PubMed Central Google Scholar - Kong, A. et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488, 471–475 (2012).
Article CAS PubMed PubMed Central Google Scholar - Michaelson, J.J. et al. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell 151, 1431–1442 (2012).
Article CAS PubMed PubMed Central Google Scholar - Howie, B.N., Donnelly, P. & Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 5, e1000529 (2009).
Article CAS PubMed PubMed Central Google Scholar - Lao, O. et al. Correlation between genetic and geographic structure in Europe. Curr. Biol. 18, 1241–1248 (2008).
Article CAS PubMed Google Scholar - Novembre, J. et al. Genes mirror geography within Europe. Nature 456, 98–101 (2008).
Article CAS PubMed PubMed Central Google Scholar - Ralph, P. & Coop, G. The geography of recent genetic ancestry across Europe. PLoS Biol. 11, e1001555 (2013).
Article CAS PubMed PubMed Central Google Scholar - Bhatia, G., Patterson, N., Sankararaman, S. & Price, A.L. Estimating and interpreting _F_ST: the impact of rare variants. Genome Res. 23, 1514–1521 (2013).
Article CAS PubMed PubMed Central Google Scholar - Zheng, H.-X., Yan, S., Qin, Z.-D. & Jin, L. MtDNA analysis of global populations support that major population expansions began before Neolithic Time. Sci. Rep. 2, 745 (2012).
Article CAS PubMed PubMed Central Google Scholar - Abdellaoui, A. et al. Population structure, migration, and diversifying selection in the Netherlands. Eur. J. Hum. Genet. 21, 1277–1285 (2013).
Article CAS PubMed PubMed Central Google Scholar - Lao, O. et al. Clinal distribution of human genomic diversity across the Netherlands despite archaeological evidence for genetic discontinuities in Dutch population history. Investig. Genet. 4, 9 (2013).
Article CAS PubMed PubMed Central Google Scholar - Novembre, J. & Stephens, M. Interpreting principal component analyses of spatial population genetic variation. Nat. Genet. 40, 646–649 (2008).
Article CAS PubMed PubMed Central Google Scholar - Gusev, A. et al. Whole population, genome-wide mapping of hidden relatedness. Genome Res. 19, 318–326 (2009).
Article CAS PubMed PubMed Central Google Scholar - Palamara, P.F., Lencz, T., Darvasi, A. & Pe'er, I. Length distributions of identity by descent reveal fine-scale demographic history. Am. J. Hum. Genet. 91, 809–822 (2012).
Article CAS PubMed PubMed Central Google Scholar - Gratten, J., Visscher, P.M., Mowry, B.J. & Wray, N.R. Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease. Nat. Genet. 45, 234–238 (2013).
Article CAS PubMed Google Scholar - MacArthur, D.G. et al. Guidelines for investigating causality of sequence variants in human disease. Nature 508, 469–476 (2014).
Article CAS PubMed PubMed Central Google Scholar - Boettger, L.M., Handsaker, R.E., Zody, M.C. & McCarroll, S.A. Structural haplotypes and recent evolution of the human 17q21.31 region. Nat. Genet. 44, 881–885 (2012).
Article CAS PubMed PubMed Central Google Scholar - Jia, X. et al. Imputing amino acid polymorphisms in human leukocyte antigens. PLoS ONE 8, e64683 (2013).
Article CAS PubMed PubMed Central Google Scholar - Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589–595 (2010).
Article PubMed PubMed Central Google Scholar - Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
CAS PubMed PubMed Central Google Scholar - Ye, K., Schulz, M.H., Long, Q., Apweiler, R. & Ning, Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25, 2865–2871 (2009).
Article CAS PubMed PubMed Central Google Scholar - Chen, K. et al. BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat. Methods 6, 677–681 (2009).
CAS PubMed PubMed Central Google Scholar - Abyzov, A., Urban, A.E., Snyder, M. & Gerstein, M. CNVnator: an approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. Genome Res. 21, 974–984 (2011).
Article CAS PubMed PubMed Central Google Scholar - Coe, B.P., Chari, R., MacAulay, C. & Lam, W.L. FACADE: a fast and sensitive algorithm for the segmentation and calling of high resolution array CGH data. Nucleic Acids Res. 38, e157 (2010).
Article CAS PubMed PubMed Central Google Scholar - Marschall, T., Hajirasouliha, I. & Schönhuth, A. MATE-CLEVER: Mendelian-inheritance-aware discovery and genotyping of midsize and long indels. Bioinformatics 29, 3143–3150 (2013).
Article CAS PubMed PubMed Central Google Scholar - Handsaker, R.E., Korn, J.M., Nemesh, J. & McCarroll, S.A. Discovery and genotyping of genome structural polymorphism by sequencing on a population scale. Nat. Genet. 43, 269–276 (2011).
Article CAS PubMed PubMed Central Google Scholar - Li, R. et al. De novo assembly of human genomes with massively parallel short read sequencing. Genome Res. 20, 265–272 (2010).
CAS PubMed PubMed Central Google Scholar - Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457–465 (1981).
Article CAS PubMed Google Scholar - Andrews, R.M. et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet. 23, 147 (1999).
Article CAS PubMed Google Scholar - van Oven, M. & Kayser, M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum. Mutat. 30, E386–E394 (2009).
Article PubMed Google Scholar - Excoffier, L. & Lischer, H.E.L. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol. Ecol. Resour. 10, 564–567 (2010).
Article PubMed Google Scholar - Ewing, B., Hillier, L., Wendl, M. & Green, P. Base-calling of automated sequencer traces using Phred. I. Accuracy assessment. Genome Res. 8, 175–185 (1998).
Article CAS PubMed Google Scholar - Ewing, B. & Green, P. Base-calling of automated sequencer traces using Phred. II. Error probabilities. Genome Res. 8, 186–194 (1998).
Article CAS PubMed Google Scholar - Wijaya, E., Frith, M.C., Suzuki, Y. & Horton, P. Recount: expectation maximization based error correction tool for next generation sequencing data. Genome Inform. 23, 189–201 (2009).
PubMed Google Scholar - Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
CAS PubMed Google Scholar - Habegger, L. et al. VAT: a computational framework to functionally annotate variants in personal genomes within a cloud-computing environment. Bioinformatics 28, 2267–2269 (2012).
Article CAS PubMed PubMed Central Google Scholar - Reumers, J. et al. SNPeffect: a database mapping molecular phenotypic effects of human non-synonymous coding SNPs. Nucleic Acids Res. 33, D527–D532 (2005).
Article CAS PubMed Google Scholar - Adzhubei, I., Jordan, D.M. & Sunyaev, S.R. Predicting functional effect of human missense mutations using PolyPhen-2. Curr. Protoc. Hum. Genet. Chapter 7, Unit 7.20 (2013).
- Cooper, G.M. et al. Distribution and intensity of constraint in mammalian genomic sequence. Genome Res. 15, 901–913 (2005).
Article CAS PubMed PubMed Central Google Scholar - Pruitt, K.D. et al. RefSeq: an update on mammalian reference sequences. Nucleic Acids Res. 42, D756–D763 (2014).
Article CAS PubMed Google Scholar - Browning, B.L. & Yu, Z. Simultaneous genotype calling and haplotype phasing improves genotype accuracy and reduces false-positive associations for genome-wide association studies. Am. J. Hum. Genet. 85, 847–861 (2009).
Article CAS PubMed PubMed Central Google Scholar - Delaneau, O., Marchini, J. & Zagury, J.-F. A linear complexity phasing method for thousands of genomes. Nat. Methods 9, 179–181 (2012).
Article CAS Google Scholar - Drmanac, R. et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327, 78–81 (2010).
Article CAS PubMed Google Scholar - Huisman, M.H.B. et al. Population based epidemiology of amyotrophic lateral sclerosis using capture-recapture methodology. J. Neurol. Neurosurg. Psychiatry 82, 1165–1170 (2011).
Article PubMed Google Scholar - Howie, B., Marchini, J. & Stephens, M. Genotype imputation with thousands of genomes. G3 1, 457–470 (2011).
Article PubMed PubMed Central Google Scholar - Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).
Article CAS PubMed Google Scholar - Browning, B.L. & Browning, S.R. A fast, powerful method for detecting identity by descent. Am. J. Hum. Genet. 88, 173–182 (2011).
Article CAS PubMed PubMed Central Google Scholar - Palamara, P.F. & Pe'er, I. Inference of historical migration rates via haplotype sharing. Bioinformatics 29, i180–i188 (2013).
Article CAS PubMed PubMed Central Google Scholar - Ward, J.H. Hierarchical grouping to optimize an objective function. J. Am. Stat. Assoc. 58, 236–244 (1963).
Article Google Scholar - Palamara, P.F., Lencz, T., Darvasi, A. & Pe'er, I. Length distributions of identity by descent reveal fine-scale demographic history. Am. J. Hum. Genet. 91, 809–822 (2012).
Article CAS PubMed PubMed Central Google Scholar - Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
Article CAS PubMed PubMed Central Google Scholar - Cockerham, C.C. & Weir, B.S. Covariances of relatives stemming from a population undergoing mixed self and random mating. Biometrics 40, 157–164 (1984).
Article CAS PubMed Google Scholar
Acknowledgements
We wish to dedicate this work to the memory of David R. Cox, an enthusiastic supporter of human genetic research in the Netherlands for many years. The GoNL Project is funded by the BBMRI-NL, a research infrastructure financed by the Netherlands Organization for Scientific Research (NWO project 184.021.007). We acknowledge additional financial support from eBioGrid, CTMM/TraIT, the Ubbo Emmius Fund, the Netherlands Bioinformatics Center (NBIC) and EU-BioSHARE. We thank the individual participants of the biobanks; M. Depristo, E. Banks, R. Poplin and G. del Angel from the Broad Institute for expert advice on setting up our alignment and calling pipeline; K. Garimella for the initial implementation of PhaseByTransmission; G. Strikwerda, W. Albers, R. Teeninga, H. Gankema and H. Wind of the Groningen Center for Information Technology (see URLs) for support of the compute cluster and Target storage; E. Valentyn and R. Williams of Target (see URLs) for hosting project data on IBM GPFS storage; T. Visser and I. Nooren of BiG Grid (see URLs) and SURFsara for providing backup storage, additional computing capacity and expert advice; the team from MOLGENIS (see URLs) for software development support; H. Lauvenberg for handling data access requests; K. Zych for design of the GoNL logo; L. Franke, H.-J. Westra and J. Gutierrez-Achury for useful discussions; and S. Raychaudhuri and B. Neale for their critical reading of the manuscript. Target is supported by Samenwerkingsverband Noord Nederland, the European Fund for Regional Development, the Dutch Ministry of Economic Affairs, Pieken in de Delta and the provinces of Groningen and Drenthe. Target operates under the auspices of Sensor Universe. BiG Grid and the Life Science Grid are financially supported by the Netherlands Organization for Scientific Research (NWO). A.A. is funded by the Center for Medical Systems Biology-2, and D.I.B. is funded by the European Research Council (ERC 230374). A.S. and P.I.W.d.B. are recipients of VIDI awards (NWO projects 016.138.318 and 016.126.354, respectively).
Author information
Author notes
- LifeLines Cohort Study and Paul I W de Bakker: A full list of members appears in the Supplementary Note.
- David R Cox: Deceased.
- Laurent C Francioli, Androniki Menelaou, Sara L Pulit and Freerk van Dijk: These authors contributed equally to this work.
- Paul I W de Bakker, Morris A Swertz and Cisca Wijmenga: These authors jointly directed this work.
Authors and Affiliations
- Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
Laurent C Francioli, Androniki Menelaou, Sara L Pulit, Clara C Elbers, Wigard P Kloosterman, Jessica van Setten, Isaäc J Nijman, Ivo Renkens & Paul I W de Bakker - Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Freerk van Dijk, Pieter B T Neerincx, Patrick Deelen, Alexandros Kanterakis, Martijn Dijkstra, Heorhiy Byelas, K Joeri van der Velde, Mathieu Platteel, Morris A Swertz & Cisca Wijmenga - Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Freerk van Dijk, Pieter B T Neerincx, Patrick Deelen, Alexandros Kanterakis, Martijn Dijkstra, Heorhiy Byelas, K Joeri van der Velde, Morris A Swertz & Cisca Wijmenga - Department of Computer Science, Columbia University, New York, New York, USA
Pier Francesco Palamara & Itsik Pe'er - The Genome Institute, Washington University, St. Louis, Missouri, USA
Kai Ye - Department of Medical Statistics and Bioinformatics, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Kai Ye, Eric-Wubbo Lameijer, Matthijs H Moed, Marian Beekman, Anton J M de Craen, H Eka D Suchiman & P Eline Slagboom - European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Victor Guryev - Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands
Abdel Abdellaoui, Jouke Jan Hottenga, Mathijs Kattenberg, Gonneke Willemsen & Dorret I Boomsma - Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Elisabeth M van Leeuwen, Lennart C Karssen, Najaf Amin, Fernando Rivadeneira, Aaron Isaacs, Albert Hofman, André G Uitterlinden & Cornelia M van Duijn - Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Mannis van Oven & Manfred Kayser - Department of Human Genetics, Leiden Genome Technology Center, Leiden University Medical Center, Leiden, the Netherlands
Martijn Vermaat, Jeroen F J Laros & Johan T den Dunnen - Netherlands Bioinformatics Center, Nijmegen, the Netherlands
Martijn Vermaat, Jeroen F J Laros, David van Enckevort & Hailiang Mei - Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
Mingkun Li & Mark Stoneking - Department of Clinical Epidemiology, Bioinformatics Laboratory, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands
Barbera D C van Schaik - SURFsara, Science Park, Amsterdam, the Netherlands
Jan Bot - Centrum Wiskunde & Informatica, Life Sciences Group, Amsterdam, the Netherlands
Tobias Marschall & Alexander Schönhuth - Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
Jayne Y Hehir-Kwa - Center for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
Jayne Y Hehir-Kwa - Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Robert E Handsaker, Paz Polak, Mashaal Sohail, Dana Vuzman, Karol Estrada, Steven A McCarroll & Shamil R Sunyaev - Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
Robert E Handsaker & Steven A McCarroll - Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Paz Polak, Mashaal Sohail, Dana Vuzman & Shamil R Sunyaev - Department of Genome Sciences, University of Washington, Seattle, Washington, USA
Fereydoun Hormozdiari - Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Vyacheslav Koval, Fernando Rivadeneira, Karol Estrada, Carolina Medina-Gomez & André G Uitterlinden - Department of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
Karol Estrada - Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Ben Oostra - Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands
Jan H Veldink & Leonard H van den Berg - Rinat-Pfizer, Inc., South San Francisco, California, USA
Steven J Pitts, Shobha Potluri, Purnima Sundar & David R Cox - Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Johan T den Dunnen - Department of Human Genetics, Forensic Laboratory for DNA Research, Leiden University Medical Center, Leiden, the Netherlands
Peter de Knijff - BGI-Shenzhen, Shenzhen, China
Qibin Li, Yingrui Li, Yuanping Du, Ruoyan Chen, Hongzhi Cao & Jun Wang - BGI-Europe, Copenhagen, Denmark
Ning Li & Sujie Cao - Department of Biology, University of Copenhagen, Copenhagen, Denmark
Jun Wang - The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Jun Wang - Legal Pathways Institute for Health and Bio Law, Aerdenhout, the Netherlands
Jasper A Bovenberg - Department of Systems Biology, Columbia University, New York, New York, USA
Itsik Pe'er - Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
Gert-Jan B van Ommen - Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
Paul I W de Bakker
Consortia
The Genome of the Netherlands Consortium
- Laurent C Francioli
- , Androniki Menelaou
- , Sara L Pulit
- , Freerk van Dijk
- , Pier Francesco Palamara
- , Clara C Elbers
- , Pieter B T Neerincx
- , Kai Ye
- , Victor Guryev
- , Wigard P Kloosterman
- , Patrick Deelen
- , Abdel Abdellaoui
- , Elisabeth M van Leeuwen
- , Mannis van Oven
- , Martijn Vermaat
- , Mingkun Li
- , Jeroen F J Laros
- , Lennart C Karssen
- , Alexandros Kanterakis
- , Najaf Amin
- , Jouke Jan Hottenga
- , Eric-Wubbo Lameijer
- , Mathijs Kattenberg
- , Martijn Dijkstra
- , Heorhiy Byelas
- , Jessica van Setten
- , Barbera D C van Schaik
- , Jan Bot
- , Isaäc J Nijman
- , Ivo Renkens
- , Tobias Marschall
- , Alexander Schönhuth
- , Jayne Y Hehir-Kwa
- , Robert E Handsaker
- , Paz Polak
- , Mashaal Sohail
- , Dana Vuzman
- , Fereydoun Hormozdiari
- , David van Enckevort
- , Hailiang Mei
- , Vyacheslav Koval
- , Matthijs H Moed
- , K Joeri van der Velde
- , Fernando Rivadeneira
- , Karol Estrada
- , Carolina Medina-Gomez
- , Aaron Isaacs
- , Steven A McCarroll
- , Marian Beekman
- , Anton J M de Craen
- , H Eka D Suchiman
- , Albert Hofman
- , Ben Oostra
- , André G Uitterlinden
- , Gonneke Willemsen
- , LifeLines Cohort Study
- , Mathieu Platteel
- , Jan H Veldink
- , Leonard H van den Berg
- , Steven J Pitts
- , Shobha Potluri
- , Purnima Sundar
- , David R Cox
- , Shamil R Sunyaev
- , Johan T den Dunnen
- , Mark Stoneking
- , Peter de Knijff
- , Manfred Kayser
- , Qibin Li
- , Yingrui Li
- , Yuanping Du
- , Ruoyan Chen
- , Hongzhi Cao
- , Ning Li
- , Sujie Cao
- , Jun Wang
- , Jasper A Bovenberg
- , Itsik Pe'er
- , P Eline Slagboom
- , Cornelia M van Duijn
- , Dorret I Boomsma
- , Gert-Jan B van Ommen
- , Paul I W de Bakker
- , Morris A Swertz
- & Cisca Wijmenga
Contributions
P.I.W.d.B., D.I.B., J.A.B., C.M.v.D., G.-J.B.v.O., P.E.S., M.A.S. and C.W. (chair) formed the steering committee of the GoNL Project. Biobanks are managed and organized by A.H., A.G.U., C.M.v.D., B.O., F.R., A.I. (for the Rotterdam and Erasmus Rucphen Family studies), D.I.B., G.W. (for the Netherlands Twin Register), P.E.S., M.B., A.J.M.d.C., H.E.D.S. (for the Leiden Longevity Study) and the members of the LifeLines Cohort Study. P.I.W.d.B. and M.A.S. jointly led the analysis group. Sequencing data were generated at BGI (Shenzhen, China) by Q.L., Y.L., Y.D., R.C., H.C., N.L., S.C. and J.W. Additional Complete Genomics sequencing data were generated by S.J.P., S.P., P.S. and D.R.C. through a partnership with Pfizer. F.v.D., P.B.T.N., P.D., L.C.F., A.K., M.D., H.B., K.J.v.d.V. and M.A.S. formed the operational data stewardship and processing center. P.B.T.N., F.v.D. and M.A.S. designed and implemented the compute cluster. M.D., H.B., A.K. and M.A.S. designed and implemented the MOLGENIS computing platform to scale up analysis pipelines for alignment, variant calling and imputation. F.v.D. and L.C.F. performed alignment with help from I.J.N., J.B. and B.D.C.v.S. L.C.F. and F.v.D. called SNVs. L.C.F., S.L.P., A.M., E.M.v.L., L.C.K., M. Sohail, A.A. and M.V. performed quality control. V.G., K.Y., L.C.F., T.M., A.S., R.E.H., S.A.M., W.P.K., F.H., J.Y.H.-K., E.-W.L., A.A., V.K., H.M., M.H.M. and J.B. formed the structural variation subgroup. L.C.F. developed the PhaseByTransmission module in GATK and performed de novo mutation analyses with P.P. A.M. performed haplotype phasing and imputation benchmarks. J.H.V. and L.H.v.d.B. provided Complete Genomics data for imputation benchmarking. W.P.K. and I.R. performed variant validation. C.W. and M.P. generated Immunochip data on all GoNL samples. S.L.P., C.C.E., A.M., P.F.P., I.P., A.A., N.A., M. Sohail, D.V. and S.R.S. performed population genetic analyses. M.v.O., M.V., M.L., J.F.J.L., M. Stoneking, P.d.K. and M. Kayser performed mitochondrial DNA analysis. P.D., A.M., A.K., E.M.v.L., L.C.K., K.E., C.M.-G., J.v.S., M. Kattenberg, J.J.H. and D.v.E. formed the imputation subgroup. P.B.T.N., K.J.v.d.V. and M.A.S. were responsible for the GoNL website and associated services (see URLs). C.W. conceived the GoNL Project. P.I.W.d.B. wrote the initial manuscript with critical input from L.C.F., A.M., S.L.P., P.F.P. and C.C.E. C.W., D.I.B., G.-J.B.v.O., L.C.K., A.A., M.A.S., P.E.S., S.R.S., J.Y.H.-K., I.P., J.H.V., P.d.K., W.P.K., T.M., A.S., V.G., J.T.d.D. and M. Kayser provided critical feedback on the manuscript. All authors have seen and approved the final manuscript.
Corresponding authors
Correspondence toPaul I W de Bakker or Cisca Wijmenga.
Ethics declarations
Competing interests
The author declare no competing financial interests.
Supplementary information
Source data
Rights and permissions
About this article
Cite this article
The Genome of the Netherlands Consortium. Whole-genome sequence variation, population structure and demographic history of the Dutch population.Nat Genet 46, 818–825 (2014). https://doi.org/10.1038/ng.3021
- Received: 10 October 2013
- Accepted: 06 June 2014
- Published: 29 June 2014
- Issue Date: August 2014
- DOI: https://doi.org/10.1038/ng.3021